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Fig. 1 | Acta Neuropathologica Communications

Fig. 1

From: Review of RyR1 pathway and associated pathomechanisms

Fig. 1

a Group 1. 1) RyR1 open (voltage-gated): RyR1 activation in response to DHPR activation by acetylcholine (ACh) release at the neuromuscular junction in skeletal muscle 2) RyR1 closed: no neuromuscular-stimulated ACh release. b Group 2. 1) RyR1 open: No interdomain interaction (unzipped) with bound ApoCaM in response to RyR1 activation preceded by DHPR activation resulting in high sarcoplasmic Ca2 + 2) RyR1 closed: bound Ca2+-Cam at high [Ca2+] resulting in interdomain interaction (zipped) and high sarcoplasmic reticulum (SR) Ca2+. c Group 3. 1) RyR1 open: RyR1-triadin interaction due to triadin-calsequestrin (CSQ) interaction at high Ca2+ bound CSQ resulting in high sarcoplasmic Ca2+ 2) RyR1 closed: RyR1-junctin interaction due to junctin-CSQ interaction at low Ca2+ bound CSQ in phosphorylated state  resulting in high SR Ca2+. d Group 4. 1) RyR1 open: RyR1 and Gm phosphorylation by PKA due to high [cAMP] resulting in high sarcoplasmic Ca2+ 2) RyR1 closed: RyR1 dephosphorylation by PP1 due to low [cAMP] resulting in high SR Ca2+. e Group 5. S-nitrosylation. 1) RyR1 open: nitrosylation of RyR1 cysteine residues by nitric oxide-glutathione reaction in response to physiologic p(O2)  resulting in high sarcoplasmic Ca2+2) RyR1 open: nitrosylation of RyR1 by nitric oxide overrides Ca-CaM inhibitory effect resulting in high sarcoplasmic Ca2+ S-oxidation. 1) RyR1 open: oxidation of RyR1 cysteine residues by reactive oxygen species reaction in response to increased physiologic p(O2) resulting in high sarcoplasmic Ca2+ 2) RyR1 closed: no RyR1 oxidation at low physiologic p(O2) with bound Ca2+-CaM resulting in high SR Ca2+ S-glutathionylation. 1) RyR1 open: initial increase in reduced glutathione (GSH) stimulating glutathionylation of RyR1 cysteine residues by GSH, in turn, decreasing the GSH:GSSG and reducing RyR1 sensitivity to Mg2+ inhibition resulting in high sarcoplasmic Ca2+ 2) RyR1 closed: no glutathionylation until GSH:GSSG ratio is restored resulting in high SR Ca2+ S-palmitoylation. 1) RyR1 open: palmitoylation of RyR1 cysteine residues by the fatty acid palmitoyl-CoA resulting in high sarcoplasmic Ca2+2) RyR1 closed: no palmitoylation resulting in high SR Ca2+. f Group 6. 1) RyR1 open: RyR1-ligand (Ca2+and ATP) binding activation resulting in high sarcoplasmic Ca2+ 2) RyR1 closed: RyR1-ligand (Ca2+ and Mg2+) binding deactivation resulting in high SR Ca2+

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